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J Steroid Biochem Mol Biol. 2002 Dec;83(1-5):37-48.

Molecular mechanisms of glucocorticoid action and resistance.

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  • 1Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, 111 Alexander Drive, P.O. Box 12233, Research Triangle Park, NC 27709, USA.


The actions of glucocorticoid hormones are mediated by an intracellular receptor, the glucocorticoid receptor (GR). The mechanism of action of this ligand-inducible transcription factor is discussed, focusing on mechanisms of glucocorticoid resistance. Three mechanisms are highlighted: ligand-induced down-regulation of the receptor, the dominant-negative inhibition by the beta-isoform of the receptor, and repression by the transcription factor NF-kappa B. It has been shown that these mechanisms can significantly inhibit glucocorticoid signaling, and could therefore seriously decrease the efficacy of glucocorticoids used clinically.

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